In industrial countries, about 98% of the adult population exhibits one or more carious lesions or are already provided with fillings. Any carious lesion which eventually may lead to cavitation is initiated by demineralization of the hard tooth substance. At an early stage, referred to as “initial enamel caries”, the tooth surface remains intact without visible signs of erosion but the demineralized area below the surface becomes more and more porous.
Today, the only non-operative ways to treat approximal caries are to enhance remineralization by application of fluorides and to arrest lesion progress by improvement of patient's oral hygiene. While smooth surfaces of the tooth are more susceptible for improved cleaning strategies, approximal surfaces are particularly difficult to clean. Nevertheless, remineralization in approximal lesions that have reached the dentin seems to be hardly achievable, since several clinical studies showed that from this threshold a visible cavitation of the lesion is established in most cases (Rugg-Gunn A J. Approximal carious lesions. A comparison of the radiological and clinical appearances. Br Dent J, 1972, 133:481-484; De Araujo F B et al. Diagnosis of approximal caries: radiographic versus clinical examination using tooth separation. Am J Dent, 1992, 5:245-248; Ratledge et al. A clinical and microbiological study of approximal carious lesions. Part 1: The relationship between cavitation, radiographic lesion depth, the site-specific gingival index and the level of infection of the dentine. Caries Res, 2001, 35:3-7). Moreover, in vitro studies even found many cavitations in lesions confined to enamel. A cavitated enamel lesion cannot be cleaned sufficiently by the patient and will progress (Marthaler T M and Germann M. Radiographic and visual appearance of small smooth surface caries lesions studied on extracted teeth. Caries Res, 1970, 4:224-242; Kogon S L et al. Can radiographic criteria be used to distinguish between cavitated and noncavitated approximal enamel caries? Dentomaillofac Radiol, 1987, 16:33-36). Therefore, if a cavitation occurs even at such an early stage of the caries process, a remineralization seems very unlikely under clinical conditions. This could explain clinical findings, that fluoridation and improved oral hygiene can only slow down the progression of approximal caries but are not capable of reversing it (Mejare I et al. Caries development from 11 to 22 years of age: A prospective radiographic study. Prevalence and distribution. Caris Res, 1998, 32:10-16).
Once a cavitation has developed, invasive methods of treatment are generally indicated. However, drilling out carious tooth material is always accompanied by the removal of non-carious, i.e. sound, hard tooth substance. In approximal carious lesions which are difficult to reach, the ratio of carious and intact substance being removed is particularly unfavorable. Moreover, the connection between an inserted filling and the endogenous tooth material is susceptible for carious lesions itself, and renewal of fillings due to the ageing process leads to further removal of sound tooth material. Therefore, methods of treating caries at an early stage, and in particular approximal initial carious lesions, are highly desirable in order to prevent later requirement for invasive procedures.
One apparent indication of initial enamel caries are white spot lesions. Such a lesion is characterized by a loss of mineral in the bulk of enamel, whereas the surface of the lesion remains relatively intact (so-called “pseudo-intact surface layer”). A promising approach of non-operative dentistry might be the sealing of enamel lesions with low viscous light curing resins such as dental adhesives and fissure sealants. The tiny pores within the lesion body act as diffusion pathways for acids and dissolved minerals and, therefore, enable the dissolution of enamel at the advancing front of the lesion. The aim of the proposed regimen is not only to seal the surface but to infiltrate these pores, thereby withdrawing the lesion body from further attack. Moreover, after curing the resin material, a mechanical support of the fragile enamel framework in the lesion will be achieved. Therefore, an occlusion of the pores by infiltration with light curing resins might arrest the lesion progression and mechanically stabilize the fragile lesion structure.
The idea to arrest caries by sealing with low viscous resins has been followed in several in vitro experiments since the seventies of the last century (Robinson C et al. Arrest and control of carious lesions: A study based on preliminary experiments with resorcinol-formaldehyde resin. J Dent Res, 1976, 55:812-818; Davila J M et al. Adhesive penetration in human artificial and natural white spots. J Dent Res, 1975, 54:999-1008; Gray G B and Shellis P. Infiltration of resin into white spot caries-like lesions of enamel: An in vitro study. Eur J Prosthodont Restor Dent, 2002, 10:27-32; Garcia-Godoy F et al. Caries progression of white spot lesions sealed with an unfilled resin. J Clin Pediatr Dent, 1997, 21:141-143; Robinson C et al. In vitro studies of the penetration of adhesive resins into artificial caries-like lesions. Caries Res, 2001, 35:136-141; Schmidlin P R et al. Penetration of a bonding agent into de- and remineralized enamel in vitro. J Adhes Dent, 2004, 6:111-115). It could be shown that sealants can penetrate the body of artificial lesions nearly completely (Gray G B and Shellis P. Infiltration of resin into white spot caries-like lesions of enamel: An in vitro study. Eur J Prosthodont Restor Dent, 2002, 10:27-32; Meyer-Lueckel, H et al. Influence of the application time on the penetration of different adhesives and a fissure sealant into artificial subsurface lesions in bovine enamel. Dent Mater 2006, 22:22-28), and reduce the accessible pore volumes within the lesions significantly (Robinson C et al. In vitro studies of the penetration of adhesive resins into artificial caries-like lesions. Caries Res, 2001, 35:136-141). Moreover, it has been observed that sealants are capable to inhibit further lesion progress under demineralizing conditions (Robinson C et al. Arrest and control of carious lesions: A study based on preliminary experiments with resorcinol-formaldehyde resin. J Dent Res, 1976, 55:812-818; Garcia-Godoy F et al. Caries progression of whit spot lesions sealed with an unfilled resin. J Clin Pediatr Dent, 1997, 21:141 - 143; Robinson et al. In vitro studies of the penetration of adhesive resins into artificial caries-like lesions. Caries Res, 2001, 35:136-141; Muller J et al. Inhibition of lesion progression by penetration of resins in vitro: Influence of the application procedure. Oper Dent 2006, 31:338-345; Paris S et al. Progression of sealed initial bovine enamel lesions under demineralizing conditions in vitro. Caries Res, 2006, 40:124-129).
However, one of the problems in sealing natural enamel lesions is that “pseudo-intact surface layers” have higher mineral contents compared to carious bodies of lesion. As a consequence, these layers inhibit the penetration of the lesion body by the sealing material and may even function as a barrier. In the end, the surface layer may be superficially sealed, but the carious body may be insufficiently penetrated by the resin. At worst, the carious process further proceeds below the “seal”.
Efforts have been made to enhance the penetration of sealants in enamel lesions. In an in vitro model, artificial enamel lesions were produced showing an intact surface layer, a body of lesion and a progressive demineralization front. It has been shown that a 5 seconds etching of those artificially induced lesions with phosphoric acid resulted in deeper penetration depths (Gray G B and Shellis P. Infiltration of resin into white spot caries-like lesions of enamel: An in vitro study. Eur Prosthodont Restor Dent, 2002, 10:27-32). Thus, such a pre-treatment or “conditioning” of an enamel area by etching could also improve the penetration of sealant in vivo. However, artificially induced enamel lesions differ from natural lesions in that they comprise regular and relatively thin “pseudo-intact surface layers”. Natural enamel lesions, in contrast, usually show higher mineralized surface layers of varying thickness. Thus, conditioning with phosphoric acid, although demonstrated as successful in vitro, must not necessarily provide for a benefit in vivo.
WO 00/09030 discloses a teeth-coating method that protects teeth from caries and peridontal diseases along with giving color to them. This coating method consists of the steps of (a) etching the teeth, for example by acid or laser; (b) application of a protective substance to the etched teeth; and (c) sealing the teeth. For acid etching, commonly employed materials such as phosphoric acid, maleic acid, citric acid and pyruvic acid are mentioned.
Nevertheless, an in vivo study reported that the application of a conventional adhesive onto enamel lesions pre-treated with phosphoric acid gel resulted in retardation of caries progression compared to controls (Martignon et al. Caries Res, 2006, 40:382-388). However, patients were monitored for two years only and diagnosis was done by X-raying, a rather insensitive method for analyzing successful penetration. Therefore, the results of this study should be regarded with some caution, as even the authors concede. Moreover, it remains unclear whether this initial success would be seen after longer periods since the rather superficial “seal” might be destroyed due to the physical load in vivo.
In the previous studies only commercially available adhesives and fissure sealants which have been optimized for adhesive purposes have been used to penetrate subsurface enamel lesions. Composite resins optimized to rapidly infiltrate these enamel lesions (“infiltrants”) might achieve better sealing results. In order to develop such composite resins, a better understanding of the processes occurring during the penetration of enamel lesions is needed.
Physically, the penetration of a liquid (uncured resin) into a porous solid (enamel lesion) is described by the Washburn equation (Equation 1, see below). This equation assumes that the porous solid is a bundle of open capillaries (Buckton G. Interfacial phenomena in drug delivery and targeting. Chur, 1995); in this case, the penetration of the liquid is driven by capillary forces.
                              d          2                =                              (                                                            γ                  ·                  cos                                ⁢                                                                  ⁢                θ                                            2                ⁢                                                                  ⁢                η                                      )                    ⁢                      r            ·            t                                                        -                ⁢        Equation        ⁢                                  ⁢        1        ⁢                  -                                    d distance, moved by the liquid resin        γ surface tension of the liquid resin (to air)        θ contact angle of the liquid resin (to enamel)        η dynamic viscosity of the liquid resin        r capillary (pore) radius        t penetration time        
The bracketed term of the Washburn equation is the penetration coefficient (PC, Equation 2, see below) (Fan P L et al. Penetrativity of sealants. J Dent Res, 1975, 54:262-264). The PC is composed of the liquid's surface tension to air (γ), the cosine of the liquid's contact angle to enamel (θ) and the dynamic viscosity of the liquid (η). The higher the coefficient is, the faster the liquid penetrates a given capillary or porous bed. This means that a high PC can be achieved for high surface tensions, low viscosities and low contact angles where the influence of the contact angle is comparatively low.
                    PC        =                  (                                                    γ                ·                cos                            ⁢                                                          ⁢              θ                                      2              ⁢                                                          ⁢              η                                )                                              -                ⁢        Equation        ⁢                                  ⁢        2        ⁢                  -                                    PC penetration coefficient        γ surface tension of the liquid resin (to air)        θ contact angle of the liquid resin (to enamel)        η dynamic viscosity of the liquid resin        
Previously, a positive correlation between the penetration coefficients (PCs) of commercial sealants and their ability to penetrate into fissures could be found (O'Brien W J et al. Penetrativity of sealants and glazes. The effectiveness of a sealant depends on its ability to penetrate into fissures. Oper Dent, 1987, 3:51-56). Moreover, low viscouse sealants showed deeper penetration when applied on etched enamel (Irinoda Y et al. Effect of sealant viscosity on the penetration of resin into etched human enamel. Oper Dent 2000, 25:274-282). However, no study has hitherto focused on the influence of the PC on resin penetration into carious lesions. The penetration of five commercially available adhesives and one fissure sealant into artificial enamel lesions was subject of a recent study (Meyer-Lueckel, H et al. Influence of the application time on the penetration of different adhesives and a fissure sealant into artificial subsurface lesions in bovine enamel. Dent Mater, 2006, 22:22-28). The penetration depth was shown to depend on penetration time. In this study, the best performing commercially available material Excite® penetrated 105 μm in 30 seconds and completely filled artificial enamel lesions. The square correlation between penetrated depth and time arising from the Washburn equation (see Equation 1) showed that enormous penetration times are needed if a deep infiltration of natural lesion (>1000 μm) is aimed with commercially available materials. This underlines the need for faster penetration composites. However, application times of more than 120 seconds are hardly acceptable for use in a dentist's daily practice due to economical reasons.
Thus, there is still a strong need for improved non-operative procedures of treating initial or even advanced enamel lesions in order to inhibit caries progression.
It is therefore an object of the present invention to provide for methods and means enabling improved resin penetration of initial or advanced enamel lesions.